Malaria has been and remains a major infectious disease. It is caused by protozoan parasites of the genus Plasmodium. Plasmodium falciparum, one of four species infectious to humans, causes the most severe and fatal disease. Despite the numerous drugs which had been used to control malaria, the growing threat of drug resistance forms has created an urgent requirement for new therapeutic modalities.
The blood stage infection which is entirely responsible for the symptoms of malaria, begins with the entry of a merozoite into the erythrocyte. The intra-erythrocytic parasite develops through morphologically distinct ring (0-24 h)and trophozoite (24-36 h) stages to schizogony (36-48 h), where mitosis occurs and 10-16 daughter merozoites are assembled. At the end of schizogony the infected erythrocyte ruptures and the released merozoites reinvade red cells to maintain the asexual cycle.
It is known that P. falciparum sphingomyelin synthase and ERD2 (a receptor for protein retention in the endoplasmic reticulum (ER)) are localized in distinct compartments of the Golgi, which is different from the situation in mammalian cells. While the ER is reorganized by the drug brefeldin A, unlike PfERD2 in P. falciparum, the sphingomyelin synthase site is not reorganized by brefeldin A, indicating that its dynamics are altered in the parasite system.
As distinct from mammalian cells, sphingomyelin biosynthetic activity in P. falciparum has unique features of secretion, such as the development of a tubovesicular membrane reticulum (TVM) beyond the parasite plasma membrane in the cytoplasm of the erythrocyte and the export of a fraction of the sphingomyelin synthase biosynthetic activity to these membranes. The possibility of interfering with the development of the tubovesicular membrane reticulum opens up avenues for therapeutic approaches to the treatment of malaria.